Facteurs associés au sepsis sévère et au choc septique

1. Facteurs associés au sepsis sévère et au choc septique Dr RamziJeddi

2. Etudes antérieures réalisées

5. facteurs prédictifs de choc septique FactorsUnivariateanalysis p OR Pulmonary infection 0.001 17 Pseudomonasspecies 0.014 13 Serum Bicarbonate< 17 <0.001 68 Serum lactate > 3 <0.001 63

6. facteurs prédictifs de choc septique FactorsMulitivariateanalysis p OR Pulmonary infection 0.043 5 Serum lactate 0.003 10

7. - Incidence élevée d’ infection due au Pseudomonas -Mortalité à j 28 = 35% (par choc septique) Monitoring: lactate & bicarbonate Colistin + β-lactamin

8. Utilisation de colistin IV? 3 études du 43rd ICAAC (USA) 2003 1-Polymixin B in the treatment of multidrugresistant Gram-negative infection . ALH KWA et al.Singapore General Hospital 2-Efficacy and safety of polymixin B in the treatment of infection caused by multidrugresistant Gram-negativeorganisms. Sobieszczyk ME et al ,NY. 3-Treatment of nosocomial infections caused by multidrug-resistantAcinetobacterbaumannii and Pseudomonasaeruginosawithintravenouscolistin. Siddiqui TJ et al. Loyola University.

9. Utilisation de colistin IV? Efficacité de la colistine iv : Pseudomonas & Acinetobactermultirésistants faible incidence d’insuffisance rénale

10. Utilisation de Colistine IV? Profil de résistance dansnotre service Fréquence (%) Résistance (%) IMP CTZ CIP AMK E Coli 14 - 45 26.3 21.3 Klebsiella 9.1 - 84.8 - - Pseudomonas 7.5 50 50.6 51.5 54.5

11. Valeur pronostiquede PCT semi-quantitative : Etude prospective de 50 épsodes PCT > 0.5ng/ml (p=0.004) CRP > 100 mg/ml (p=0.008) PCT > 10 ng/ml (p=0.017) Lactate > 3 mmol/L (p=0.04) Infection documentée Choc septique

12. Facteurs associés au sepsis sévèreEtude prospective de 95 épisodes neutropéniques fébriles score radiologique Hb HR/SBP Lactate RR Bicarbonate SaO2 PCT Bilirubine CRP AntibiotherapiePhosphatémie Hypocalcémie Fibrinémie Severe sepsis

13. Episode neutropénique fébrile et état septique Neutropenic febrile episode °C 1 2 24H ANC<0.5 °C 1 ANC<0.5

14. Episode neutropénique fébrile et état septique Severe sepsis °C 1 2 24H D(ANC<0.5) °C 1 D(ANC< 0.5)

19. Caractéristiques de l’étude Patients n 41 age,median,range 28 (3-58yr) sex,M,F 25,16 underlyingdisease AML,n 21 ALL,n 19 MCL,n 1 Chemotherapy MRC 10 21 Hyper CVAD 10 EORTC 58951 9 BEAM 1 Neutropenia Episodes,n 95 Duration,median,range 12 (7-28 d) 22 severe sepsis

20. Protocoled’antibiothérapie Piperacillin/Tazobactam + Colistin 48-72h Amphotericin B Imipenem 48-72h Vancomycin,Teicoplanin (IDSA* criteria) Décontamination digestive Colimycin+ Gentamycin 17/41 compliant Severe Sepsis *Hughes WTetal.Clin Infect Dis. 2002 Mar 15;34(6):730-51

21. Caractéristiques de 95 épisodes Documentés microbiologiquement,n (%) 27 (28.7) Gram- ,n (%) 13 (48.1) Pseudomonas1 Klebsiella5 Acinetobacter1 Alcaligenes2 Ochtrobacterium2 Stenotrophomonas 1 E.Coli1 Gram+ ,n (%)11(40.7) Staphylococcus10 streptococcus1 Mixed,n (%) 3 (11.1) Documenté cliniquement,n (%) 5 (5.3) cutaneous 1 Pulmonary 2 Typhlitis 1 Sinusitis 1 Non Documenté,n (%) 62 (65.9)

22. profil de résistance aux antibiotiques N.of isolates tested (16) Antibiotic resistant (%) Piperacillin/tazobactam 62.5 Imipenem 6.3 Ciprofloxacin 6.3 Ceftazidim 50 Amikacin 25 Colistin 0

23. Susceptibility of infecting agents species,n Resistance to (%) Oxacillin Staphylococcus 13 83.9 Amoxicillin Streptococcus 1 1/1

24. Facteurs associés au sepsis sévère Facteurs p* odds ratio (95% CI) Hypophosphatémie < 0.8 mmol/l 0.05 3.9 (1.3-45.7) Hypoproteinémie< 62g/L 0.006 4.1 (1.4-11.4) Antibiothérapie non adaptée 0.019 2.7 (1.0-7.3) *Fisher exact test

25. Hypophosphatemia? incidence of Hypophosphatemia (%) Hospitalized patients 2.2 – 3.1 Admitted to ICU 28.8 – 33.9 Sepsis 65- 80 Chronicalcoholism 2.5- 30.4 Major trauma 75

26. Etiology of hypophosphtemia in septic shock .Previous phosphate depletion .Transcellular shifts in relation to glucose,insulin and cathecholamin infusions .Increased anaerobic glycolysis

27. Threepotentialdeleteriouseffects of hypophosphatemiathatcouldbe of primary importance in sepsis Decreasedmyocardial contractility 1

28. Threepotentialdeleteriouseffects of hypophosphatemiathatcouldbe of primary importance in sepsis DecreasedmyocardialImpairedresponse to contractilityvasopressor agents 1 2

29. Threepotentialdeleteriouseffects of hypophosphatemiathatcouldbe of primary importance in sepsis DecreasedmyocardialImpairedresponse to DecreasedOxygen contractilityvasopressor agents delivery to tissues 3 1 2

31. Hypophosphatémie mécanisme de survenue dans le sepsis? Quel est l’effet d’une correction sur l’évolution?

32. Hypoproteinemia? . Intensive cytotoxic treatment Highest energy Expenditure at d14 Protein-losing Enteropathy Negligible oral intake Malnutrution Hypoproteinemia Serum Albumin <2.5/L

33. Hypoproteinemia? criticalillness Increasedmicrovascularpermeability to proteins Increasedtranscapillary escape of serumprotein Albumin ++ Shift of fluidfromintrvascularintointerstitialcompartment hypovolemia=major component of hypotension seen in sepsis

34. Albumin supplementation sufficient to nearly double serum concentrations in profoundly hypoalbuminemic septic patients Had no clinically significant effect in reducing microvascular permeability Pas d’effet de l’apport d’albumine

35. Antibiothérapie adaptée

36. Antibiothérapie adaptée

37. Antibiothérapie adaptée? 1H 80% 2154 hypotensive Septic shock patients Received effective antibiotherapy 2H Survival 3H - 7.6% 4H 5H 42% 6H

38. Golden Hour Silver day

40. Facteurs non associés au sepsis sévère Facteursp odds ratio (95%CI) RythmeCardiaque/ PA systolique < 1.10.0010.1 ( 0.03-0.31) C reactive protein < 80 mg0.001 0.14 (0.04-0.54)

41. Heart rate/Systolic blood pressure< 1.1 ?

46. Heart rate/Systolic blood pressure< 1.1 ?

47. C-reactive protein The test for CRP is a simple and effective screening test for occult bacterial infection or tissue injury Young B, Gleeson M, Cripps AW. C-reactive protein: a critical review.Pathology 1991;23:118–24.

50. Hb< 8g/dl and Gram -?